(UroToday.com) The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on the importance of lifestyle and prevention of complications in advanced prostate cancer, and a presentation by Dr. Heather Cheng discussing how we should take care of our patient’s muscle strength. Dr. Cheng started her presentation by highlighting that across the prostate cancer disease spectrum, ADT is utilized as a backbone for a significant portion of treatment:
Sarcopenia, the age-related phenomenon of muscle loss, is associated with ADT use. We know that serum testosterone correlates with greater muscle and less fat, and loss of muscle + increased subcutaneous and visceral abdominal fat is a well-recognized side effect of ADT. Loss of muscle strength increases with frailty, worsens physical functioning, and increases fall risk and disability.
ADT has lasting consequences, especially in older patients. Smith et al.1 prospectively evaluated lean body mass in a prespecified sub-study of a randomized controlled trial of denosumab to prevent fractures in men receiving ADT for nonmetastatic prostate cancer. The metric of lean body mass was measured by total-body DEXA imaging at study baseline and at 12, 24, and 36 months. Patients were also stratified by age (< 70 vs ≥ 70 years) and by ADT duration (≤ 6 vs > 6 months). Men aged ≥ 70 years (n = 127) had significantly greater changes in lean body mass at all measured time points than younger men, and at 36 months lean body mass decreased by 2.8% in men aged≥ 70 years and by 0.9% in younger men (p = 0.04). Men with ≤ 6 months of ADT at study entry (n = 36) had a greater rate of decrease in lean body mass compared with men who had received more than 6 months of ADT at study entry (3.7% vs 2.0%; p = 0.06):
Thus, Dr. Cheng questions “if we see these changes with 6 months of ADT, what is the impact of longer duration and more profound androgen receptor suppression?” Fischer and colleagues2 analyzed the effects of enzalutamide on skeletal muscle/subcutaneous fat and compared the results with abiraterone in patients with mCRPC among 17 patients starting abiraterone and 37 patients starting enzalutamide. This study found a significant loss of skeletal muscle compared to baseline observed for enzalutamide (mean loss 5.2%, p<0.0001) and abiraterone (mean loss 3.0%, p = 0.02), with no effect on subcutaneous fat and no difference between treatments:
Dr. Cheng mentioned one particular study of interest, the PC170059 study assessing the role of mitochondria in ADT-induced sarcopenia in prostate cancer patients. This study will enroll 60 patients with histologically or image documented metastatic prostate cancer initiating ADT with expected continuous treatment for a minimum of 6 months who will be followed for at least 6 months. The primary outcome is lean body mass change measured by DEXA scan, and secondary outcomes will be as follows:
- Hand grip strength, stair climb power, VO2 max, daily physical activity change (actigraphy)
- Skeletal muscle mitochondrial function (in vivo) assessed by magnetic resonance spectroscopy
- Skeletal muscle mitochondrial function (ex vivo) assessed by oxygen consumption rate
- Quality of life changes measured by EORTC QLQ-C30 and EPIC
Dr. Cheng notes that it is important for our patients to undergo resistance and aerobic exercise training. Combined resistance and aerobic exercises help reverse muscle loss in patients on ADT, with preliminary studies noting that 12 weeks of training among men with prostate cancer on ADT led to improvements in lean body mass, muscle strength and function, cardiovascular capacity, and improved quality of life. Additionally, we should be starting these patients on programs early and offering our support. Among men planned for ADT, 3 months of supervised aerobic + resistance training (2x/week for 60 minutes), followed by 3 months of self-directed exercise versus usual care led to improvements in fat mass at 3 months. Additional noted patient benefits for those starting ADT and commencing workout programs include improved general health at 6 weeks and improved mental health.
A study that is being supported by Movember and is an important lifestyle trial that is ongoing is the INTERVAL-GAP4 trial. This is a randomized controlled phase 3 study for men with mCRPC (n = 866) and a primary objective of determining if high intensity aerobic and resistance training (supervised exercise) + psychological support increases overall survival compared to psychological support alone. Secondary objectives include PFS, time to first symptomatic SRE, time to progression of pain, assessing biomarkers for inflammation, and energy metabolism.
As follows is a table highlighting select ongoing clinical trials of exercise intervention in advanced prostate cancer:
Dr. Cheng has specific points/questions that she discusses with her patients when they are starting ADT:
- Ask them what they do and meet them where they are
- Share the data: physical, quality of life, and survival benefits
- Invite goal setting: “Can you do 20% more?” “That’s great that you have such a strong cardio practice, can you incorporate resistance training?”
- Social exercise has better uptake and follow through: refer patients for a clinical trial, physical therapy, supports groups, and video education
- Ask again, encourage, celebrate, and reinforce
Dr. Cheng concluded her presentation by discussing taking care of muscle strength among our prostate cancer patients with the following take-home messages:
- ADT can lead to sarcopenia even after a short course of treatment (~6 months). These negative effects are further compounded with deep androgen receptor suppression with abiraterone, enzalutamide, etc
- Exercise, especially aerobic and resistance, can mitigate these negative findings
- Early intervention with the start of ADT may be better, but some are better than none, and we should be enrolling these patients in clinical trials whenever possible (ie. INTERVAL-GAP4 and others)
- Lifestyle changes require different approaches than prescribing medications but can have a comparable positive impact
- Medical approaches are being studied, but please do not wait for these results to take action with your patients
- Be your patient’s advocate and sponsor, meet them where they are, motivate them, enroll them in clinical trials and support them (physical therapists, caregivers, support groups)
Dr. Cheng provided one final thought to conclude her presentation, noting that with earlier use of next generation androgen receptor blockade and longer overall survival, attention to survivorship with advanced prostate cancer is more important than ever. Our job is improving quality of life, not just delay death.
Presented by: Heather H. Cheng, MD, PhD, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Annual Hybrid Meeting, Lugano, Switzerland, Thurs, Apr 28 – Sat, Apr 30, 2022.
References:
- Smith MR, Saad F, Egerdie B, et al. Sarcopenia during androgen-deprivation therapy for prostate cancer. J Clin Oncol. 2012 Sep 10;30(26):3271-3276.
- Fischer S, Clements S, McWilliams A, et al. Influence of abiraterone and enzalutamide on body composition in patients with metastatic castration resistant prostate cancer. Cancer Treat Res Commun. 2020;25:100256.